Pilot study of oxygen transport rate of banked red blood cells

Background and Objectives  Dynamic oximetry provides a new way to assess the effect of blood storage on the oxygen transport rate (OTR).
Materials and Methods  In dynamic oximetry, the rate at which oxyhemoglobin becomes deoxyhemoglobin is measured optically, thereby, indirectly measuring the rate at which oxygen leaves the red blood cell (RBC) making it available for transfer to tissues. Extending the physiologic diffusion time in an in vitro apparatus, consisting of a diffusion system and gas exchanger capable of controlling the surface area and the time of exposure for oxygenation and deoxygenation, makes OTR measurement feasible. Eight normal blood donor units, collected in adenine, dextrose, sorbitol, sodium chloride and mannitol , were stored for 8 weeks under standard conditions and serially sampled for OTR.
Results  We report that the OTR at the time of blood bank donation appears to be singular for each donor, that the interdonor differences are maintained over time, and that the individual OTR increased 1·72-fold (95% CI 1·51, 1·95) over 8 weeks, adjusting for sex, age and plasma cholesterol level.
Conclusion  Oxygen transport rate increases during storage; blood units with similar haemoglobin content may have significant differences in OTR. Studies examining blood parameters at the time of donation and blood storage on patient outcomes should consider measuring OTR, as it may contribute to differences in observed efficacy of tissue oxygenation.     

Soft drug design: general principles and recent applications

Soft drug design represents a new approach aimed to design safer drugs with an increased therapeutic index by integrating metabolism considerations into the drug design process. Soft drugs are new therapeutic agents that undergo predictable metabolism to inactive metabolites after exerting their therapeutic effect. Hence, they are obtained by building into the molecule, in addition to the activity, the most desired way in which the molecule is to be deactivated and detoxified. In an attempt to systematize and summarize the related work done in a number of laboratories, including ours, the present review presents an overview of the general soft drug design principles and provides a variety of specific examples to illustrate the concepts. A number of already marketed drugs, such as esmolol, remifentanil, or loteprednol etabonate, resulted from the successful application of such design principles. Many other promising drug candidates are currently under investigation in a variety of fields including possible soft antimicrobials, anticholinergics, corticosteroids, beta-blockers, analgetics, ACE inhibitors, antiarrhythmics, and others. Whenever possible, pharmacokinetic and pharmacodynamic properties are briefly summarized and compared to those of other compounds used in the same field.     

Cerebrospinal fluid leak from nontumor ear after acoustic neuroma surgery: diagnostic and therapeutic problems.

An unusual case of CSF leak from the nontumor ear after removal of a 3-cm acoustic neuroma is presented. Prior to tumor removal a ventricular-peritoneal shunt was established because of increased intracranial pressure. After the shunt was clamped the patient twice developed rhinoliquorrhea and underwent in both instances unsuccessful closure of the leak on the tumor side. Finally the leak was established in the nontumor ear, most likely due to sequelae after a hunting accident 20 years before, where a projectile created a defect in the tegmen tympani. The CSF leak was probably provoked by the pressure changes following tumor removal and shunt treatment.     

Inverted papilloma: a follow-up study including primarily unacknowledged cases

Inverted papillomas (IPs) in the nose or the paranasal sinuses exhibit a tendency for rapid growth with bone destruction, a high recurrence rate, and an association with malignancy, requiring early diagnosis and aggressive surgical therapy. A number of operative approaches have been reported in the literature, with greatly varying results. Furthermore, the incidence of IP and the association with carcinoma are not well-established. In this study, we present a series of 42 patients with IP. Drawing from the resources of two institutes of pathology, we reviewed all specimens of nasal cavity or paranasal sinus tissue taken between the years 1975 and 1986, and performed a thorough follow-up of all IP patients. The incidence was found to be 0.6 cases per 100,000 inhabitants per year in a well-defined representative geographic region. Two patients had concomitant carcinoma. When the initial surgical approach was lateral rhinotomy, the recurrence rate was 50%. This was not significantly different from that noted following excision through a sinusectomy (62%) or simple endonasal excision (43%). However, initial procedures were selected individually, mainly on the basis of tumor size and location. Accordingly, a limited procedure is considered justified even in cases with lateral lesions, if the tumor is sufficiently visible and confined. In other cases, lateral rhinotomy is required. Septal IPs are often detected at an early stage and are therefore often amenable to local excision.     

Immunity to hepatitis B, poliomyelitis and measles in fully vaccinated Aboriginal and Torres Strait Island children

Objective: To determine the immunity to hepatitis B, poliomyelitis and measles in fully vaccinated Aboriginal and Torres Strait Island children in north Queensland.
Methodology: A cross-sectional survey of immunity in a sample of children; 101 fully vaccinated Aboriginal and Torres Strait Island children, with a median age of 24.5 months, from 10 communities in North Queensland participated in this study. The main outcome measures were the prevalence of adequate antibody levels against hepatitis B, poliomyelitis and measles.
Results: Only 54% (95% Cl 44–63%) of the children had adequate immunity (10 m iu/mL) to hepatitis B, and one child had been infected despite vaccination. Although all the children (95% Cl 96–100%) had adequate immunity (i.e. neutralizing antibodies at a dilution of 1:8) to poliovirus 2, only 93% (95% Cl 86–96%) and 60% (95% Cl 50–69%) had adequate immunity to polioviruses 1 and 3, respectively. Nearly all (96%; 95% Cl 90–98%) of the children had adequate immunity (i.e. detectable IgG antibody) to measles.
Conclusions: Although a relatively low proportion of the children had adequate antibody levels against hepatitis B the clinical significance of this observation is uncertain. Further studies are needed to determine whether fully vaccinated Torres Strait Island children have been adequately protected and whether they require a booster dose of hepatitis B vaccine. A substantial proportion of fully vaccinated Aboriginal and Torres Strait Island children are inadequately protected against poliomyelitis, and therefore any such child with acute flaccid paralysis should be investigated fully for poliomyelitis. Vaccinated Aboriginal and Torres Strait Island children are well protected against measles, as are other Australian children.     

Human papillomavirus (HPV) in sinonasal papillomas: A study of 78 cases using in situ hybridization and polymerase chain reaction

To determine the role of human papillomavirus (HPV) in the etiology of sinonasal papillomas, 57 inverted papillomas including 5 cases associated with carcinomas, 16 exophytic papillomas, and 5 cases of columnar cell papillomas were examined for the presence of HPV DNA by in situ hybridization and polymerase chain reaction (PCR). The genetic studies were performed on the formalin-fixed, paraffin-embedded material. In only 6% of the 52 benign inverted papillomas was HPV DNA identified, whereas 69% of the exophytic papillomas were infected by HPV DNA. In none of the 5 cases with columnar cell papillomas could HPV be demonstrated. HPV 6/11 was identified in all of these HPV-positive cases. In the carcinoma area, HPV was detected in 2 (1 HPV 6/11 and 1 HPV 18) of the 5 inverted papillomas associated with carcinomas. The findings confirm the presence of HPV DNA in sinonasal papillomas. The results also indicate that HPV 6/11 may be involved in the pathogenesis of, solely, exophytic papillomas. We found that in situ hybridization and PCR seem equally sensitive in detecting HPV in sinonasal papillomas.     

Barriers to remember: brain-targeting chemical delivery systems and Alzheimer's disease

Brain-targeted chemical delivery systems (CDSs) represent rational drug design attempts not only to deliver but also to target drugs to their site of action. Using a sequential metabolism approach, the special bidirectional properties of the blood-brain barrier can be exploited to smuggle the precursors of therapeutic compounds across the barrier and lock them inside the brain ready for sustained release of the active drugs. Many potential therapeutic applications can be envisioned for such CDSs; here, the potential of brain-targeted estradiol for the prevention and treatment of Alzheimer's disease is reviewed in detail.     

Chronic diffuse musculoskeletal pain,fibromyalgia and co-morbid unexplained clinical conditions

This chapter reviews our current knowledge on the presence of overlapping syndromes in one form of chronic diffuse pain, fibromyalgia. Patients with fibromyalgia often present with signs and symptoms of other unexplained clinical conditions, including chronic fatigue syndrome, irritable bowel syndrome, temporomandibular disorders, and multiple chemical sensitivities. The high prevalence, impact on function and opportunities for treatment underscore the need for clinicians and researchers to screen routinely for co-morbid unexplained clinical conditions among persons with fibromyalgia. We, therefore, describe a simple approach to screening for such conditions in accordance with published criteria. Interventions should directly address both fibromyalgia symptoms and co-morbid unexplained clinical conditions, as well as the multiple factors that propagate pain, fatigue and limitations in function.